Natural Gelatin Capped Mesoporous Silica Nanoparticles for Intracellular Acid-Triggered Drug Delivery

Abstract

This paper proposed a natural gelatin capped mesoporous silica nanoparticles (MSN@Gelatin) based pH-responsive delivery system for intracellular anticancer drug controlled release. In this system, the gelatin, a proteinaceous biopolymer derived from the processing of animal collagen, was grafted onto the MSN to form a capping layer via temperature-induced gelation and subsequent glutaraldehyde mediated cross-linking, resulting in gelatin coated MSN. At neutral pH, the gelatin capping layer could effectively prohibit the release of loaded drug molecules. However, the slightly acidic environment would lead to enhanced electrostatic repulsion between the gelatin and MSN, giving rise to uncapping and the subsequent controlled release of the entrapped drug. As a proof-of-concept, doxorubicin (DOX) was selected as the model anticancer drug. The loading and pH-responsive release experiments demonstrated that the system had excellent loading efficiency (47.3 mmol g(-1) SiO2), and almost no DOX was leaked at neutral. After being in the slightly acidic condition, the DOX release from the DOX-loaded MSN@Gelatin (DOX/MSN@Gelatin) occurred immediately. The cellular uptake and release studies using Hep-G2 hepatoma cells indicated that the DOX/MSN@Gelatin could be endocytosed and accumulated within lysosomes. Triggered by acidic endosomal pH, the intracellular release of the loaded DOX was obviously eventuated. Further cell viability results demonstrated that DOX/MSN@Gelatin exhibited dose-dependent toxicity and high killing efficacy (IC50 = 17.27 ± 0.63 μg mL(-1)), whereas the MSN@Gelatin showed negligible cytotoxicity (IC50 > 100 μg mL(-1)). This biocompatible and effective delivery system will provide great potential for developing delivery of cancer therapeutic agents.

Using hyaluronic acid-functionalized pH stimuli-responsive mesoporous silica nanoparticles for targeted delivery to CD44-overexpressing cancer cells

“…5,9,20,23 Briefly, 2.4 g of CTAB was dissolved in deionized water (800 mL) with vigorous stirring at 80°C. Then 3.6 mL of NaOH (2 mol/L) was dissolved into the solution and stirred vigorously for 2 continual hours.…”

“…7,8 The MSNs system is an extremely robust nanoparticle system used for drug delivery; recent studies also supported the use of MSNs as a delivery system for hydrophobic anticancer drugs to overcome their insolubility problem. 9 When these nanomaterials are developed as drug delivery systems, drawbacks are encountered such as drug leakage, 10 nonspecific targeting effects, 11 difficulties in monitoring cellular events after drug delivery, etc. 12 Therefore, the design and development of smart drug delivery systems with multiple functions, such as simultaneous stimuli-responsive drug release and targeting to tumor cell, are becoming increasingly urgent.…”

Zeolitic Imidazolate Framework-8 Capped Mesoporous Silica Nanoparticles for pH-Controlled Drug Release

“…[18][19][20] To date, much effort has been made to develop pH-triggered drug release systems using MSN as nanocarriers. [21][22][23][24][25][26][27] For example, Zou et al proposed a natural gelatin capped MSN for intracellular anticancer drug controlled release. 21 The gelatin capping layer could effectively block drug release at neutral pH, but the slightly acidic environment triggered drug release due to the enhanced electrostatic repulsion between the gelatin and MSN, resulting in uncapping of the gelatin layer.…”

“…[21][22][23][24][25][26][27] For example, Zou et al proposed a natural gelatin capped MSN for intracellular anticancer drug controlled release. 21 The gelatin capping layer could effectively block drug release at neutral pH, but the slightly acidic environment triggered drug release due to the enhanced electrostatic repulsion between the gelatin and MSN, resulting in uncapping of the gelatin layer. 21 Chen et al used i-motif quadruplex DNA to cap the mesopores of MSN and realized pH-controlled drug release based on the morphology change of the DNA chains.…”

“…21 The gelatin capping layer could effectively block drug release at neutral pH, but the slightly acidic environment triggered drug release due to the enhanced electrostatic repulsion between the gelatin and MSN, resulting in uncapping of the gelatin layer. 21 Chen et al used i-motif quadruplex DNA to cap the mesopores of MSN and realized pH-controlled drug release based on the morphology change of the DNA chains. 22 Huang et al prepared graphene quantum dots (GQDs) grafted MSN nanocarriers (GQDs-MSN) through electrostatic interaction, and in vitro assay showed the release of aspirin from the aspirin-loaded GQDs-MSN was pH-dependent.…”